Method &amp; device for making reversed bypass with cultured vessel in situ

ABSTRACT

A method of using reversed bypass for physiologically reducing vessel resistance and increasing blood supply to an ischemia area in a living human, comprises a new use of microsurgery punching device for making a hole or flap in an equivalent of 10μ-1 mm by caliber diameter in plane and 1-600μ in depth on lateral walls of small artery and vein with an attachable connection. The connection includes a) a vivid blood flow, b) a lumen or two holes on vessel walls, c) an extra-vascular glue, wrapping cuff, or attachable tube, supporting the blood flow as vessel wall and enhancing the endothelium to line over the interior surface of the connection as a cultured vessel in situs. Endothelium adhesion and growth factor, blood circulation inducers, and anti-coagulation agent are added to enhance such new bypass formation.

BACKGROUND OF THE INVENTION

1. Technical Field

The disclosure relates, in general, to reversed bypass microsurgery, andmore particularly to a method and device for physiologically reducingvessel resistance and increasing blood supply in mammal ischemia areawith cultured vessel in situs

2. Description of the Related Art

Vascular bypass surgery has been widely used to correct vessel stenosis,which is based on sutured anastomosis and availability of graft forsubstituting a narrowed artery. However, those skilled in the art arestill currently confronted with particularly difficult problem cases.(U.S. Patent issued to Miyata et al U.S. Pat. No. 4,098,571 forheterograft substitute blood vessel; to Chanda et al U.S. Pat. No.5,645,587 for prevention of calcification and degeneration of implantedgrafts; to Katsuen et al U.S. Pat. No. 5,691,203 for serum-free cultureof human vascular endothelia cells; to Horiguchi U.S. Pat. No. 5,755,779for blood stream adjuster, to Edelman et al U.S. Pat. No. 5,766,584 forinhibition of vascular smooth muscle cell proliferation with implantedmatrix containing vascular endothelial cells; to Epstein et al U.S. Pat.No. 5 951,589 for expansile device for use in blood vessels; to KrajicekU.S. Pat. No. 5,968,089 for internal shield of a anastomosis; toRateliffet al U.S. Pat. No. 5,968,090 for a endovascular graft andmethod; to Kranz U.S. Pat. No. 5,968,093 for a stent comprising at leastone thin walled, tubular member). In particular, high vessel resistantcases speed up the narrowing process. Consequently, even with the use ofstents, maximum permitted blood supply does not last long enough andbypass surgery may have to be done repeatedly.

It is difficult to suture vessels having a caliber or diameter smallerthan 0.2-mm and a stent requires even bigger caliber to be inserted.Autografts are not always available and cultured heterograft vessels cancause rejection. It is thus a surprise to provide a blood flow asleading force for the vascular endothelium to grow as cultured in situwithout suture, which breaks the lower limitation of vessel caliberrequirement. In addition, full transfer of arterial pressure waveresults in damage and intimal hyperplasia to the vein at the anastomosisand subsequent occlusion or thrombosis as in conventional bypass. Thesmaller the artery is and the less pressure and structure differenceexists between the artery and vein, the better the outcome can be. Theearlier the collateral bypass can be established, the longer thepreventive effect can be achieved.

DETAILED DESCRIPTION OF THE INVENTION

To overcome the defects inherited from prior art, e.g., shortage ofgrafts, relapse after surgery, trauma of stent, size limitation forsuture and stent, the application modifies bypass technique as close tophysiology as possible and thus reduces recurrent risk. Since dynamicforce of blood flow leads angiogenesis and neovascularization, suture isnot necessary. As newly formed budding and sprouting from vessels needtime to age, the chance of stenosis and obstruction of newly formedvessel are lowered. Plus, veins are usually spared from artery stenosisand hypertension, and therefore the disclosure provides a novel approachto further reduce stenosis. In addition, to solve hyperdisplasia, A-Vaneurysm, and obstruction consequence following prior art, thedisclosure divides only 20-70% blood flow from artery system intoadjacent vein system, which reduces not only tissue ischemia caused byartery or arteriole obstruction but also reduces long-term vesselresistance, which contributes to hypertension and high relapse rate inconventional bypass surgery.

Upon dynamics review of blood flow in human, main blood pressure andvessel resistance are raised by small artery (>50μ), arterioles (50-20μ)and precapillary sphincter at metarteriole (10-15μ). In the fingers andpalms, there are short channels that connect arterioles to venules,bypassing the capillaries. These arteriovenous (A-V) anastomoses, orshunts, have thick, muscular walls and are abundantly innervated,presumably by vasoconstrictor nerve fibers (William G. Ganong, Review ofMedical Physiology, p 550-553, 1999). However, although the disclosureconnects a small artery to a small vein also, it acts to increasecapillary blood flow rather than to steal blood from lower reaches ofsupplied area. The vein under the A-V connection is opened to smallartery so that the blood in the small artery will flow in increasedcross-sectional channels whereas the vein at the connection is closedand therefore blood return above this point is not disturbed. The methodmakes A & V from

The artery under the A-V connection is not sutured as in conventionalanastomosis, instead, there is no trauma. Because of the volumereduction in the artery system, its blood flow after the bypass willconfront at least 20% less resistance. The blood supply in the previousvein system should confront very little or no resistance. Since thetotal cross sectional area of venule is close to the sectional area ofcapillaries that is 10 times bigger than small arteries and arterioles,activating 10% by volume reserved venule system, by theory, would coverall small artery supplied area with physiologic function reserved inmaximum. Of course the new growth vessel is supposed to be innervated bythe nerve arose from the budding of small artery side and to inheritsmall artery characteristics like a young vessel does. Furthermore,since some precapillary sphincter has been bypassed, the resistance toischemia tissue and blood pressure are reduced. Therefore, the risk ofrecurrent stenosis is greatly reduced and consequently long-term successafter surgery is increased.

It is worth noticing how a vessel hemorrhage turns into a new vessel.Since neovascularization has been the last stage due to the cause ofsevere hypoxemia, microaneurysm is actually an attempt for more bloodsupply, where red blood cells come from the up side of the artery andexist on lower side depending on the pressure gradient created thereofIf the neck is too small for the two, single red blood cell will comeand leave one by one in order to keep the circuit, which implies how thebody struggles for every red blood cell to come through, . Rather thansealing the neck of a microaneurysm, the application means to activateunused vein compensative system to subside insufficient artery supply.In reverse to reducing neovascularization, vascular endothelium growthis enhanced. Since endothelium has a growth peak about 3-7^(th) dayafter a surgery, the release of neovascularization enhancers is designedto stop as soon as the endothelium has covered the blood flow. When ablood stream flows in a groove, channel, or artificial frame, vascularendothelial cells most likely grow and reach another blood streamsuccessfully. After a bleeding continuously strikes on a point ofanother vessel's wall, the wall being stricken will open and accept theflow from the bleeding artery. Microaneurysms are formed when thebleeding whirls in loose tissue stria until exhausted at the center ofthe whirl. Under the condition of hypoxemia or stress, a blood streammay not clot as normal vessel does. Since accelerated formation ofneovascularization usually occurs near wound borders, factors present inwound healing may enhance the formation of revascularization insusceptible tissue.

In summary, the invention is a method of using a reversed bypass beingcapable of physiologically reducing mammal vessel resistance and bloodpressure, and increasing blood supply and perfusion to an ischemiatissue, area, or organ. The method comprises:

selecting a small narrow artery which is responsible to a localischermia tissue, area, or organ,

selecting a small vein which is adjacent to such artery and can bespared from vein blood return, multiple vein lateral system, or volumeconserve vein system, wherein such vein being capable of drawing bloodfrom such ischemia area,

connecting such artery with such vein and vein network so that at least20% by volume blood in the artery or arteriole is lead into vein networkthrough such vein and therefore resistant adjustment of the vessel isremained whereas total resistant is reduced,

providing a pressure gradient in such connection so that the directionof blood flow in the vein will be constantly reversed.

Particularly, the mammal is a human who has vascular disorder orischemia tissue, area, or organ. Since the use of such bypass was neverrecognized, the device and connection of the solution therefore areunobvious over prior record.

According to general human vessel data, the wall thickness of 30μ-lumendiameter arteries is about 20μ and the thickness of 30μ veins is only3μ. It is desirable for the microsurgery punch device to create a smallorifice, hole or flap in a range of equivalent of 10μ-1 mm caliberdiameter in plane and 1-600μ in depth on the wall of small vein. Theoperative end of the device comprises a tapered ending tip ormicropipette having a central area or opening approximately 1-10μ. Theenergy source is selected from the group including laser, reversed deepultraviolet wave, and ultrasound having energy sufficient to free gapand tight junction of cells to create a hole like opening on vesselwall. A 193 nm argon excimer laser-like device is ideal to interact withvessel wall in a photochemical rather than a thermal mode so that mostenergy of the photon goes to free the gap, bond, and junction ratherthan heat the surrounding. Currently, “ArF excimer laser” has principalapplication in the field of refractive surgery to ablate layers of thecornea fibers for vision correction (Lewis et al.: Method & a device forcold laser microsurgery with highly localized tissue removal, U .S. Pat.No. 5,288,288, 1994) (Freeman et al., High resolution, high speed,programmable laser beam modulating apparatus for microsurgery, U.S. Pat.No. 5,624,437, 1997). Since the transparency of vessel wall is lowerthan cornea, the goal of the present microsurgery punching device is tofree gap, bond, and junction of cells without thermal damage and toavoid abating layers of fibers. The advantage to do so is because tofree one cell will free all surroundings and therefore a smooth hole canbe created with least damage. When glue holds opposite walls of anartery and a vein next to each other, the orifice or pass on the lateralwall complex of such vessels is a mirror to each other. Preferably, theconnection is absorbable and therefore these two vessels can go backclose to its original position. Hopefully, when the distance isincreased, the endothelium growth will follow. By working cooperatively,the hole making device and the absorbable connection create a new bypassas an expected result.

When a laser microbeam or reversed ultraviolet is making a lateralopening through vessel walls, punctured debris is sucked into the deviceor forming a flap to prevent the debris dropped into vessels. The areaof removed muscle layer is bigger than the hole to prevent hyperplasiaand obstruction. Endothelium is cut as a circle or a flap. Cutaneouscatheter can be introduced for puncturing a hole from distance. Chemicalresolvent and gap opener, e.g., trypsin, collagenase, EDTA, heparin,erosive acid, lipolysis agent, or. a hypertonic solution, loosejunction/gap and reduces the tension of expanding. An expandable devicewith resolvent enzyme can ease the expanding of new channel.

Differentiated from prior endovascular stent, this connection offers anabsorbable extravascular cuff to support the blood stream andendothelium growth, which, of course, should not injure the endotheliumas endovascular stent does, instead, it offers an interior surface forendothelial cells to line over to form a new vessel. This connection canbe extremely short or quite long. Eventually the connection provides acultured new vessel graft in situs that does not need suture. When asmall artery and vein are sharing same sheath, the connection candirectly be a blood flow. An attachable connection means: 1) a vividblood stream, 2) a lumen, a pass or two holes for such blood stream toflow, and 3) an extra vascular glue or an attachable tube, a tissuecuff, wrap, channel, or graft with a kinking to hold its position, oronly a groove of tissue stria, which resides the blood flow. The methodincludes: 1) put or wrap a glue on each wall of small artery and vein;2) press these two vessels together so that the distance between thesetwo vessels is reduced; 3) punch a hole on the opposite side of eachlateral wall of these two vessels; 4) stick these two holes together toform a lumen; or 5) connect these two holes by attachable connectivetube, which is a temporary vessel with endothelium adhesion capacity inits interior surface and glue feature outside to seal leakages. The longconnective tube acts as extra-vascular cuff/wrapping with adhesive endsto hold vessels from

or from lateral-to-lateral. The advantage of the long connection is tobe used in both present and prior art.

The connection matrix is made of serum, collagen, gelatin, fibrin,fibronectin, carbohydrate, protein, connective tissue, glue, polymer,and synthesis compound. The connection can be further mixed, coatedwith, or being capable of releasing a pharmaceutical effective amount ofanti-coagulation agent, endothelium adhesive and growth factor, andangiogenesis agent. For example, heparin, degraded heparin, endothelialcell component, adenosine, arginine, glycine, viagra, viagra-like agent,chitosin, anti-coagulation agent, re-stenosis inhibitor, vascularendothelium growth factor, epithelium growth hormone, acidic and basicfibroblast growth factor, transforming growth factors α and β, tissuefactor, factor V, angiogenin, platelet derived endothelial cell growthfactor, IL 8, or an herb or compound which will enhance endotheliumadhesion and growth, increase the number of circulating endotheliumprecursor, or increase blood circulation. Absorbable glue is used toreduce the distance between a small artery and vein and hold therelative position of these two vessels like “><” so that a laser needlecan punch a hole (lumen) at the site where artery and vein are facingeach other laterally.

Applicants prefer the vessels appearing on the surface of ischemiatissue or organ, e.g., coronary vessels on the heart. The vessels canalso be on eye, brain, lung, spine, pancreas, gastrointestine, or amembrane, preferably the vessels can be seen directly.

Because sleep helps wound recovering, rejuvenation, and normalizingcortisol level, the method further comprises a step of providing atherapeutic effective amount of an anxiolytic drug or a hypnotic drugbeing capable of inducing or prolonging a sleep-like period, e.g. sodiumthiopental, chlorpromazine, chloral hydrate, diazepam, clonazepam,essential amino acid, valium, or combinations thereof. Sodium thiopentalis preferred due to its inducing immediate sleep, making people feellike a normal sleep.

While the whole disclosure has been described with respect to limitednumber of embodiments, it will be appreciated that many variations,modifications and other applications of the inventions may be made. Itis therefore intended that such changes and modifications be covered bythe claims appended hereto.

What is claimed is:
 1. A method of using a reversed bypass forphysiologically reducing mammal vessel resistance and increasing bloodsupply and perfusion to an ischemia tissue, area, or organ in a livinghuman, comprises: selecting a narrow artery or arteriole which isresponsible to a local ischemia tissue, area, or organ, selecting a veinor venule that is capable of drawing blood from said ischemia area andcan be spared from vein blood return, multiple vein lateral system, orvolume conserve vein system using a microsurgery device for making ahole or a flap on opposite lateral walls or wall complex of said arteryor arteriole and vein or venule, wherein said hole or flap havingequivalent of dimension approximately 10μ-1 mm in plane and 1-600μ indepth, connecting the artery or arteriole to the vein or venule so thatat least 20% by volume blood in the artery or arteriole will be leadinto the vein network while resistance adjustment of the vessel isremained but total resistance is reduced.
 2. The method of claim 1 saidmicrosurgery device further comprises: providing a tapered micropipetteor tip having a diameter less than 10μ with respect to said vessel wallfor making a hole, a circle, or a flap having equivalent of dimensionapproximately 10μ-1 mm in plane and 1-600μ in depth, providing anadjustable gas, vacuum or hook for controlling debris motion, deliveringa focused energy or resolvent agent through said pipette or tip in anamount sufficient to free or break down gap, bond, or junction of cellson a selected part of vessel wall to form a permanent blood pass from asmall artery to a small vein.
 3. The method of claim 2 wherein saidenergy is 193 nm argon laser beam.
 4. The method of claim 1 wherein saiddevice comprising a micropipette for delivering a chemical resolventagent to erode an orifice on the lateral wall of a vessel, or to loosegap, bond, or junction of a vessel for easing endothelial cells toexpand or move.